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JCE Featured Molecules
William F. Coleman Wellesley College Wellesley, MA 02481
Molecular Models of Reactants and Products from an Asymmetric Synthesis of a Chiral Carboxylic Acid May Featured Molecules Our JCE Featured Molecules for this month come from the paper by Thomas E. Smith, David P. Richardson, George A. Truran, Katherine Belecki, and Megumi Onishi (1). The authors describe the use of a chiral auxiliary, 4-benzyl-2-oxazolidinone, in the synthesis of a chiral carboxylic acid. The majority of the molecules used in the experiment, together with several of the pharmaceuticals mentioned in the paper, have been added to our molecule collection. In many instances multiple enantiomeric and diastereomeric forms of the molecules have been included. This experiment could easily be extended to incorporate various aspects of computation for use in an advanced organic or integrated laboratory. Here are some possible exercises using the R and S forms of the 4-benzyl-2-oxazolidinone as the authors point out that both forms are available commercially. Calculation of the optimized structures and energies of the enantiomers at the HF/631-G(d) level using Gaussian03 (2) produces the results shown in Table 1. Evaluation of the vibrational frequencies results in no imaginary frequencies and the 66 real frequencies are identical for the two forms. Examination of the computed IR spectra also shows them to be identical. Additionally, the Raman and NMR spectra can be calculated for the enantiomers and compared to experimental values and spectral patterns. A tool that is becoming increasingly important for assigning absolute configuration is vibrational circular dichroism (VCD). Although the vibrational spectra of an enantiomeric pair are identical, the VCD spectra show opposite signs, as shown in Figure 1. One can imagine a synthesis, using an unknown enantiomer of the chiral auxiliary, followed by calculations of the electronic and vibrational properties of all of the intermediates and the product, and determination of absolute configuration of reactants and products by comparison of experimental and computed VCD spectra.
Using a viewer capable of displaying two molecules that can be moved independently, students could more easily visualize the origin of the enantiomeric preference in the reaction between the chelated enolate and allyl iodide. Literature Cited 1. Smith, T. E.; Richardson, D. P.; Truran, G. A.; Belecki, K.; Onish, M. J. Chem. Educ. 2008, 85, 695–697. 2. Frisch, M. J. et al. GAUSSIAN 03, Revision C.02; Gaussian, Inc.: Wallingford, CT, 2004.
Supporting JCE Online Material
http://www.jce.divched.org/Journal/Issues/2008/May/abs752.html Full text (HTML and PDF) with links to cited JCE article Supplement
Find “Molecular Models of Reactants and Products from an Asymmetric Synthesis of a Chiral Carboxylic Acid” in the JCE Digital Library at http://www.JCE.DivCHED.org/JCEWWW/ Features/MonthlyMolecules/2008/May/.
The molecules added to the collection this month are: molecules used in the experiment (see page 695, scheme I) 4-benzyl-2-oxazolidinone (1) 4-dimethylaminopyridine (DMAP) sodium bis(trimethylsilyl)amide [NaN(TMS)2] chelated (Z)-enolate (3) of N-propionyl oxazolidinone allyl iodide allylated oxazolidinone (4, 5) chiral carboxylic acid (6) pharmaceuticals mentioned in the article compactin (cholesterol lowering agent) FK-506 (immunosuppressant) epothilone B (microtubule-stabilizing antitumor agent)
Table 1. Calculation of the Optimized Structures and Energies of the Enantiomers of 4-Benzyl-2-oxazolidinonea R Form Single Point Calculation
S Form Single Point Calculation
Calculation Type
SP
SP
Calculation Method
RHF
RHF
Basis Set
6-31G(D)
6-31G(D)
Charge
0
0
Spin
singlet
singlet
Total Energy
-589.29383182 a.u.
-589.29383182 a.u.
RMS Gradient Norm
0.0000000 a.u.
0.0000000 a.u.
Dipole Moment
6.0110 D
6.0110 D
aDone
752
at the Hf/631-G(D) level using Gaussian 03 (2).
Figure 1. Vibrational spectra of the R and S forms of 4-benzyl2-oxazolidinone are identical, but the VCD spectra show opposite signs.
Journal of Chemical Education • Vol. 85 No. 5 May 2008 • www.JCE.DivCHED.org • © Division of Chemical Education
